In the past few years, three-dimensional structures of about 200 small proteins and a DNA oligomers in solution have been determined. Multi-dimensional NMR, in particular two-dimensional nuclear Overhauser effect (2D NOE) spectra, when used in conjunction with distance geometry and energy refinement calculations can be used to determine the high-resolution structure of DNA fragments, small proteins and complexes. A major goal of our research is to improve the capability for determining high-resolution protein and nucleic acid structures in solution, including a depiction of their dynamic nature. To this end, we have been developing methods to obtain more accurate structural restraints (in the form of internuclear distances and torsion angles) and a greater number of structural restraints. We are currently working on determining time-averaged structures of some nucleic acids and proteins; this requires carrying out moderately time-consuming restrained molecular dynamics calculations. We are continuing development of an alternative restrained Monte Carlo method in torsion angle and helical parameter space, which we also utilize for structure determination. In addition, as we deal mostly with conformationally flexible molecules in solution, we have been exploring computational methodologies for ascertaining the dynamic nature of these molecules.